This invention relates to newly identified polynucleotide sequences, polypeptides encoded by such sequences, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. More particularly, the polypeptides of the present invention are naturally occurring splice variants of human growth hormone, hGHV-2(88) and hGHV-3(53). The invention also relates to inhibiting the action of such polypeptides.
Human growth hormone is produced in and released from the pituitary gland. hGHwt is a peptide hormone having several useful functions. One characteristic activity of human growth hormone is that it directs linear bone growth. Human growth hormone also has lactogenic activity and has been shown to be involved in metabolic processes such as lipid, nitrogen and carbohydrate metabolism. Recent studies on human growth hormone have begun to suggest that different regions of the molecule might be involved in controlling the above stated activities. Other indications of human growth hormone include its use in the treatment of hip fractures in the elderly, chronic renal insufficiency, Turner's syndrome, cancer and HIV infection and its subsequent effects.
Considerable effort has been expended in studying the human growth hormone molecule and its interaction with other cells and organs of the human body in an attempt to regulate human growth hormone's effect on these particular targets in the human body. For example, wild-type human growth hormone (hGHwt) is presently used to treat hypopituitism where not enough human growth hormone occurs naturally. Accordingly, a means by which to stimulate the natural production of human growth hormone in hypopituitism or to compete with the receptor sites of human growth hormone when a patient is subjected to hyperpituitism would be of great value, particularly in light of the fact that certain growth abnormalities are capable of being diagnosed prenatally.
Means and methods for production of human growth hormone variant proteins and to the determination of their DNA sequences and amino acid sequence of 191 amino acids by recombinant DNA technology were disclosed in U.S. Pat. No. 4,670,393 issued to Seeburg on Jun. 2, 1987, however, hitherto the present invention, there has not been disclosed two naturally occurring spliced variants of the human growth hormone polypeptide.
In one aspect of the present invention, there is provided polynucleotide DNA (or RNA) sequences encoding for naturally occurring splice variants of the human growth hormone, hGHV-2(88) and hGHV-3(53), as well as analogs and derivatives thereof, which both lack nucleotide sequences normally present in the gene which encodes for hGHwt.
In accordance with another aspect of the present invention, there is provided polypeptides which are naturally occurring splice variants of the human growth hormone, hGHV-2(88) and hGHV-3(53) which can function as an agonist and/or an antagonist for human growth hormone, as well as analogues and derivatives thereof.
In accordance with still another aspect of the present invention, there is provided a procedure for producing such polypeptide variants by recombinant DNA techniques.
In accordance with yet a further aspect of the present invention, there is provided a process for utilizing such polypeptides, or DNA sequences encoding such polypeptides for therapeutic purposes, for example stimulating the action of wild-type hGH and for inhibiting the action of wild-type hGH.
In accordance with yet another aspect of the present invention, there is provided a composition which is employed as an antagonist to such polypeptide, e.g., an antibody against such polypeptide. For example, in the treatment of hyperpituitism.
These and other aspects of the present invention should be apparent to those skilled in the art from the teachings herein.